PLEX may serve as an effective salvage treatment for severe CF manifestations, such as refractory skin ulcers or limb digital ischemia that do not respond to conventional immunosuppressive treatment, and CF should be considered in the differential diagnosis of patients with purpura or ischemic skin lesions.
Key Findings
Results
Three patients with cryofibrinogenemia (CF) and different clinical manifestations, refractory to conventional immunosuppressive therapies, were successfully treated with plasmapheresis (PLEX).
The case series was from IRCCS Policlinico San Matteo, Pavia, Italy.
The three patients presented with different clinical manifestations of CF.
All were refractory to conventional immunosuppressive therapies before PLEX.
The abstract reports the outcome as successful treatment with PLEX; no quantitative outcome data are given in the abstract.
Conclusions
The authors conclude that PLEX is an effective salvage treatment for severe CF manifestations such as refractory skin ulcers or limb/digital ischemia that do not respond to conventional immunosuppression.
This conclusion is based on the three reported cases plus a few cases in the literature.
The abstract states that PLEX 'has been reported in a few cases in the literature as a useful treatment for CF'.
Treatment of refractory symptomatic CF remains challenging.
Conclusions
CF should be considered in the differential diagnosis of patients with purpura or ischemic skin lesions.
CF is described as a rare systemic condition, often neglected.
It is characterized by reversible cold-induced precipitation of plasma components (fibrinogen, fibrin, fibronectin) that resuspend on rewarming to body temperature.
Background
The evidence base for CF treatment is limited to case reports and case series; no randomized controlled trials or guidelines exist.
The authors state that 'randomized controlled trials are lacking, and no guidelines exist.'
Current knowledge is based on case reports and case series.
Discussion
Reported management of CF includes glucocorticoids, with other agents used in more severe cases, and maintenance therapy for moderate disease with corticosteroids plus low-dose aspirin or stanozolol.
Azathioprine, rituximab, cyclophosphamide, anticoagulants, and intravenous fibrinolysis have been reported to be effective in more severe cases.
Proposed maintenance therapy for moderate disease is corticosteroids and low-dose aspirin or stanozolol.
What This Means
Cryofibrinogenemia is a rare condition in which certain blood proteins, such as fibrinogen, clump together when exposed to cold and dissolve again when the blood warms. This can cause purpura (purple skin spots), skin ulcers, and reduced blood flow to fingers or limbs. Because it is rare, it is often overlooked.
This report describes three patients treated at a hospital in Pavia, Italy. Each had a different presentation of the disease, and none improved with standard immune-suppressing drugs. All three were reported to be successfully treated with plasmapheresis, a procedure that filters the blood plasma to remove the problem proteins. The abstract does not give detailed numbers on outcomes.
This research suggests that doctors should consider cryofibrinogenemia in people with unexplained purpura or ischemic skin lesions, and that plasmapheresis may be a useful rescue option when other treatments fail. However, with only three patients and no randomized trials or formal guidelines, the evidence is limited, and the findings cannot show how well the treatment works in general.
Biglia A, Morandi V, Bartoletti A, Bozzola M, Iannone C, Cartia C, et al.. (2026). Cryofibrinogenemia - an often-neglected rare disease: a case series.. European review for medical and pharmacological sciences. https://doi.org/10.26355/eurrev_202610_38012